Rosuvastatin calcium is a clinical antihyperlipidemic drug, with a chemical name being (+)-(3R,5S)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidine-5-yl]-3,5-Dihydroxy-6(E)-calcium heptenoate (2:1), and a chemical structural formula as below:

Three preparation methods were reported in the literature as follows:
3. Publicly disclosed in CN1340052A
where P1 and P2 are protecting groups of hydroxy, and P3 is a tert-butyl group.
At the presence of a strong base, let an oxidized diphenyl[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonylamino)amino]pyrimidine-5-ylmethyl]phosphine react with 2-[(4R,6S)-6-formyl group-2,2-dimethyl-1,3-dioxa-4-yl]tert-butyl acetate, then disconnect the protecting group of dihydroxy in the product, alkalinely hydrolyze the tert-butyl ester group, and finally produce rosuvastatin calcium as a calcium salt.
In the first route, it takes a long reaction time to synthesize a phosphine (A), with a low yield and at the same time a usage of highly toxic and severely pollutive PBr3. There are many synthetic methods of its side chain (B) (U.S. Pat. No. 5,278,313, EP0319847, U.S. Pat. No. 5,399,722, U.S. Pat. No. 5,481,009, U.S. Pat. No. 5,998,633, U.S. Pat. No. 6,140,527, EP0104750, and WO0307733), but most of them have such problems as a long synthetic route (7-9 steps), most of intermediates being viscous, multiple steps of high vacuum (around 0.1 mmHg) distillation and silica gel column purification, a usage of hypertoxic potassium cyanide or sodium cyanide, a poor purity of products, unsteadiness, and difficulty in production industrialization.
4.
TBDMS is a protecting group of tert-butyl dimethyl silane.
The second route is difficult in synthesizing the side chain (D) (JP5-32680 and J. Org. Chem., 1994, 59 (25). 7849-7854), with a long route, intermediates of each step being mostly viscous, difficulty in separation and purification (need to go through multiple steps of silica gel column purification), a poor purity of products, and unsteadiness. The yield of connection of the side chain (D) to the main ring (C) is low, with a poor purity of products.
3. Publicly disclosed in WO2004/052867

In the third route, there is no synthetic method of the side chain (E), the yield of connection of the side chain to the main ring (C) is low, and multiple steps of silica gel column purification are required, with no physical constants for each intermediate, no detection methods for product purity or reaction progress, only testing results for small quantities, and no amplified data.